Do you have a genetic defect in the MTHFR gene??
What's the Big Deal About Methylation?! Update of the Popular MTHFR Blog Post… Maybe you've have a family history of heart attack or stroke… maybe you've suffered through multiple miscarriages. Or maybe you struggle with chronic migraine headaches or irritible bowel syndrome or depression. Perhaps your child or a sibling has autism. What do all these things have in common? Well, these are just some of the conditions liked to a faulty enzyme called MTHFR.
What's up with MTHFR?
MTHFR stands for methyl-tetrahydrofolate reductase, an enzyme that is responsible for the process of methylation in every cell in your body. MTHFR is a common genetic variant that causes this key enzyme in the body to function at a lower than normal rate. This can lead to a variety of medical problems. Although there are over fifty known MTHFR variants, the two primary ones are called C677T and A1298. Your doctor can order a blood test to determine if you have these genetic variants. Better yet, you can order a complete genetic profile yourself through 23andMe.
What's the big deal about methylation?
Methylation is a core process that occurs in all cells to help your body make biochemical conversions. When people with genetic mutations is MTHFR are exposed to toxins, they have a harder time getting rid of them which can cause some very serious illnesses. The methylation process is responsible for:
- Cellular Repair: synthesis of nucleic acids, production and repair of DNA and mRNA
- Detoxification and Neurotransmistter Production: interconversion of amino acids
- Healthy Immune System Function: formation and maturation of red blood cells, white blood cells & platelet production
The 677T variant is most commonly associated with early heart disease and stroke and the 1298C variant with a variety chronic illnesses, but either anomaly can cause a wide variety of health problems. The MTHFR anomaly is reported out as heterozygous or homozygous. If you are heterozygous that means you have one affected gene and one normal gene. Your enzyme activity will run at about 60% efficiency compared to a normal.
If you are homozygous or have 2 abnormal copies, then enzyme efficiency drops down to 10% to 20% of normal, which can be very serious. The worst combination is 677T/1298C in which you are heterozygous to both anomalies. Many chronic illnesses are linked to this anomaly. Fibromyalgia, irritable bowel syndrome, migraines, chemical sensitivity, frequent miscarriage and frequent blood clots are all conditions associated with MTHFR anomaly. For a great diagram of more methylation related health problems, check this out:
Glutathione is the body's primary antioxidant and detoxifier. One of the ways that MTHFR gene mutation can make you susceptible to illness is by lowering your ability to make glutathione. People with MTHFR anomalies usually have low glutathione, which makes them more susceptible to stress and less tolerant to toxic exposures. Accumulation of toxins in the body and increased oxidative stress, which also leads to premature aging.
Some conditions that may be associated with MTHFR gene mutations
- Autism
- Addictions: smoking, drugs, alcohol
- Down’s syndrome
- Frequent miscarriages
- Male and female infertility
- Pulmonary embolism and other blood clots
- Depression and anxiety
- Schizophrenia
- Bipolar disorder
- Fibromyalgia
- Chronic Fatigue Syndrome
- Chemical Sensitivity
- Parkinson’s disease
- Irritable Bowel Syndrome
- Stroke
- Spina bifida
- Migraines
- Hyperhomocysteinemia
- Breast cancer
- Atherosclerosis
- Alzheimer’s
- Multiple Sclerosis
- Myocardial Infarction (Heart Attack)
- Methotrexate Toxicity
- Nitrous Oxide Toxicity
Treatment for MTHFR
Fortunately, you can easily be tested for the MTHFR mutation. If you find out that you have one or more of the gene mutations, you can supplement with methyl-folate and methyl B12, the active forms of these B vitamins. You can also supplement with liposomal or acetyl-glutathione, the end product of the pathway. Glutathione is poorly absorbed so either the liposomal form or a precursor, called n-acetylcysteine (NAC) may be used. Some of my favorites are Thorne Research Methyl Guard Plus and 5-MTHF 1mg and 5mg.
There are prescription medicines, that also contain methyl-folate: Deplin, MetanX, CerefolinNAC are a few. Methyl B12 can also be given as shots, nasal sprays, and sublingually. The intramuscular shots are by far the most effective method and must be prescribed by your physician. The choice of nutrients will vary from patient to patient and should be done under a doctor's supervision. There is a bell-shaped optimal curve so you may not feel well with too much or too little of the appropriate supplements. Other B vitamins, such as riboflavin and vitamin B6 also play an important role. As you may have surmised, this can be quite complex and I suggest you find a functional medicine trained physician to help you sort through your needs for the different nutrients if you have a chronic health condition related to the gene mutations. It is not uncommon for patients with these genetic polymorphism's to be very sensitive to supplementation.
Patients who I recommend be screened for MTHFR mutations:
- Mood disorders: depression, anxiety, irritability, mood swings, bipolar
- Infants and children of parents with MTHFR mutations
- Family members related to someone with MTHFR mutations
- Infertility and Pre-conception care: test both man and woman
- Elevated folate (not processing to active 5-MTHF due to inability to methylate)
- Elevated homocysteine (due to low active 5-MTHF and methylcobalamin)
- Elevated s-adenosylhomocysteine (due to low active 5-MTHF and methylcobalamin)
- Elevated serum cobalamin (due to inability to methylate cyanocobalamin to methylcobalamin)
- Elevated methylmalonic acid (due to methylcobalamin deficiency)
- Patients with syndromes: IBS, multiple chemical sensitivity, fibromyalgia, Down syndrome, chronic fatigue syndrome
- Neurological disorders: Multiple sclerosis, Autism, Alzheimer’s, Epilepsy, Parkinson's
- Cancer: family history of cancer or undergoing cancer treatment
- Cervical dysplasia
- Cardiovascular risk: family history of strokes, embolisms, heart attacks, clots, hypertension
- Birth defects: cleft palate, tetralogy of Fallot, spinal bifida, midline defects
- Drug sensitivities: methotrexate, anti-seizure meds, nitrous oxide, anesthesia
If you are interested in knowing more about your genes, the 23andme gene test will be the best $99 investment you've ever spent !
More reading
Holistic Primary Care
Genetics Home Reference
Molecular Biology of MTHFR
Genetics of Homocysteine Metabolism
Homocysteine and MTHFR mutation
LiveWello Gene app
56 Comments
I am very much in agreement here, the one area I wonder about is the use of NACL as a GSH precursor. It has shown to be not very effective.My research has led me to γ-glutamylcysteine found in undenatured whey.http://www.tennishealth.biz/glutathione.htm
Great explanation and introduction, Dr. Jill!
Hi – a friend who is also a hospice nurse suggested your blog when I told her I was trying to do some research before our 7yr old daughter possibly has to have a tonsillectomy. Long story short – I am compound heterozygous (C677T and A1298C) for the mthfr mutation. We found out after on 2nd son was stillborn 6wks before his due date. Fast forward 10yrs and I’ve had 2 DVT’s, a large post op clot form in my abdomen and a stroke after our 5th child was born ( I did lovenox injections for all our pregnancies after losing our son) The stroke was 10wks post partum / 1 week after stopping the lovenox. After the last clot in my arm 2yrs ago my doctors and I decided that warafin was now needed and I take 12.5mg daily. Our oldest son is also positive for the mutation and had a strokes after each open heart surgery to correct transposition of the great arteries. He currently takes 800mg of folic acid daily. Our daughter just saw the hematologist at our children’s hospital – she has tested positive for the Lupus Anticoagulant and well as Antithrombin III Activity and MTHFR . At our initial appointment her doctor said that the MTHFR deficiency doesn’t cause any concern with the majority of hematologists – I’m not sure I agree and given my history and the fact that I had so many tests done after our loss and also after the CVA that I can’t imagine that they’ve missed something – what are your thoughts? We’ve put our daughter’s surgery on hold and will be consulting w/ her regular pediatrician regarding the chronic strep and how else we can deal with this..her surgeon has tried to reassure us that she will be fine and he plans on a 3 day admission vs. an out patient procedure.. but my husband and I are just not comfortable with having her undergo the surgery with all this new information. At a bit of a loss with all of this – any input would be appreciated.
Hi Anonymous – sorry to hear your complex story of health issues. I suggest you contact my office or find a functional medicine doctor in your area to help you and your family.
Warmly
Dr Jill
Hi Dr.Jill,
After getting a very high reading on my serum B-12 and being told it is probably from my diet when I have been diagnosed with autoimmune gastritis and Hashimoto’s< I was wondering if something was going on. I also have not been able to get out of the active stage of mono for 2.5 years. I thought I didn't have enough stomach acid to kill the Epstein Barr virus, but when I got my second high B-12 reading yesterday, I suspected there was more going on than just low stomach acid. In fact this result is contrary to low stomach acid and the inability to absorb B-12. I suspect I have an MTHFR gene defect on some level and would love to get this tested. I went to the 23 and me Gene Test website and it appears their tests for this have been temporarily discontinued. Where else might I find this test? Could my PCP who is a DO and forward thinker order this test through Quest or Labcorp? Or should I just assume I have it and start treatment myself? Signed, Scared and confused but happy to have possibly stumbled upon an answer
You can still get 23andme raw data and easy for any physician who knows SNPs to help interpret. I recommend still getting that test done and finding a functional medicine doctor in your area….
Hi, I’d like to come to your Clinic. Where do I stay and what is approx. cost.??? Thanks.
Hi Janet,
Go to https://www.jillcarnahan.com/about-us/fees/ for fee information. If you have other questions, please call the office at #303-443-9590 and they will be happy to help!
warmly
Dr Jill
Did you mean heterozygous 677T/1298C is the worst, or homozygous 677T/1298C is the worst. My son is heterozygous 677T/1298C; I haven’t been tested yet.
Hi Heidi, just to be clear having 2 abnormal copies of C677T and 2 abnormal copies of A1298C would be the worst case scenario but it is so rare that I didn’t mention it.
Hi. I am a 35 yr old female who was recently diagnosed with MTHFR mutation c677t by an ND. I am supplementing mainly with active methyl folate per ND. However, I haven’t had children yet (and would like to get pregnant sooner than later) and trying to be sure I take all precautions. Anyone in GA that you recommend for further expert knowledge in this area?
Hi Kelly,
Try searching at http://www.functionalmedicine.org for someone trained in your area.
warmly
Dr. Jill
Dr. Jill.
Hello, I know you cannot assist via blog and I live in Pennsylvania, near Scranton. Could you give me a referral of a functional medicine? I did use the web site funcionalmedicine.org the nearest was 6000 miles away. you did need to choose so I chose MD and chose IFM certified. with out MD andIFM cert lots came up. I have balance, memory/learning problems and C677T MTHFR mutation, heavy brain fog, CRS (cant remember shit), cant seem to find any doctors with knowledge or willing to learn about MTHFR. Help with choosing who to call Please.
Thanks Jeanne
Hi Jeanne,
You might try Dr. Debbie Bernstein (http://www.drbholisticmd.com) or Dr. John Neely ((717) 531-8181) or Dr. Alex Motroni ((570) 778-6466)
warmly
Dr Jill
Jeanne… I too live in Pa…closer to Binghamton,n y. I have just been diagnosed with MTHFR Mutation…I’m seeing Dr Kloss at Lourdes hospital in Binghamton.
Hello Dr Jill ,
I am a Pediatrician very interested in Functional Medicine and in MTHFR , do you know a doctor who has experience in South Florida specially with children .
Thank you ,
Bellia Jackson .
Hi Bellia,
Try searching for functional medicine trained docs by zip code at http://www.functionalmedicine.org – best wishes!
Dr Jill
Hi Jill
Do you perhaps know of a physician in the UK that could help me with this type of medicine
Thanks
Genee
Hi Genee,
Yes, my friend Michael Ash is an excellent resource in the UK and can be contacted through his website – here
Blessings
Dr Jill
Hi Dr. Jill,
Thank you for this well laid out article to understand MTHFR. I am homozygous C677C. I’ve always had high B12 on my blood tests & now I know why – my body wasn’t methylating the supplement I was taking! (I always thought the high level was a good thing, but I stand corrected.) I just ordered some methylcobalamin.
Question: my husband is negative for the mutation, but also has high B12, plus depression. Is it possible to have methylation issues without the mutation? Would the same supplements be warranted? Thanks for your fantastic work!
Hi Jenny
Usually high serum B12 means the body may be deficient in other co-factors like folate or B6 or that there is difficulty getting the B12 intracellular for various reasons. So, yes this could happen without methylation issues and there are many other SNPs like MTR and MTRR that come in to play with B12
warmly
Dr Jill
So with unusually high B12, you should take the active form of b12, plus B6 and methyl folate to correct this, am I right? Will I see my B-12 go even higher for a time then? ( My reading for B-12 is already off the charts, so they just say over the top number with an arrow, and I don’t know how much over it is, as it doesn’t give any reading over 750., just an arrow showing greater than.) All this time I thought I was lucky not to have to ever worry about b-12 shots like so many people over 60 have to take. Thank you for enlightening so many of us who have had blood clots,, mini strokes and no one could figure out why.
Jeanne.
Hi Jeanne,
High serum B12 can mean many things. You could have too much or it could be unable to get intracellular. Sometimes lack of co-factors, like B6 can cause this problem, genetic mutations in B12 receptor, or lack of lithium. This may be especially true if you test serum levels just after getting injection or oral dose.
Warmly
Dr Jil
Have MTHFR c677, a IGM of 103 also have lyme disease.Can’t seem to get answer from local Drs. in Pa .Can you offer some suggestions , can this create a problem in the future
Hi Judy
You might try this LLMD in Pennsylvania – or Search here
warmly
Dr. Jill
I have the homozygous C677T mutation. I’m 49. No issues with pregnancies. Two normal deliveries years ago. Persistent anxiety and persistent low grade depression as well as mood issues. Lack of energy even though I exercise regularly. Too much sleeping. probably some ADHD and forgetfulness. Lack of joy. Eating disorder in the past and an adult child of an alcoholic parent. Any suggestions? I live in Broward County, Fl. Thanks.
Hi Maribel,
Methylation is not the only determining factor in your health. I also suggest working with a functional trained MD to check your gut health, toxic exposures and eat a clean, unprocessed diet.
Hi Jill,
I just found out I’m C677TT, homozygous.
My naturopathic dr was wonderful at finding out what’s wrong. However, she kind of approached the meds part aggressively. She wanted me on B-12 Complex Plus 2x a day and taking Sam e supplement. After reading so much I know you have to approach the methyl vitamin part slowly. I’m only taking one B-12 complex plus every two days. I notice even then it still makes me feel anxious. I haven’t taken the Sam e yet, should I? Would it make me more anxious on a low dose like 200mg?
Hi Suzette,
You are right to proceed with caution. Every individual is different on what they tolerate so you may want to start with the B12 first and the introduce the 200mg SAMe if things remain stable. Trust your body and stop it if you don’t feel well.
warmly
Dr Jill
Hi. So 677 and 1298 which I have can cause the constant unrelenting headaches I have had for 3 years non stop?
Thanks
It could be related…
Hi Jill.
An opinion if you will please. I also have had 24/7 headache/migraines for several years. Fatigue,rashes,nausea and a general unwell feeling accompany them. Started when I was 16 weeks pregnant 4 years ago. Countless migraine meds,mri’s,lumbar punctures,CT scans,botox injections, infusions,nothing will relieve this pain central behind my nose,eyes and forehead. Recently I found out I have both mutations of mthfr one from each of my parents. Mainstream doctors write this off as mumbo jumbo. I’m left wondering if it is possible that my MTHFR could be the culprit. On rereading this I sound somewhat desperate to “blame something”. I guess I am. I’m not asking for your diagnosis via your website Jill. Just your opinion as to whether it is likely to be the cause please. I don’t want to waste more money on a yet another dead end. I hope you understand. Thank you for your help. Christie.
Hi Christie,
Most likely there is a relation between your poor methylation and gut health, detoxification, and potentially hidden infections. The MTHFR is just the foundation that aids you in these processes so optimizing methylation may help your headaches but more likely it’s bit more complicated than being 100% related to your genetics.
warmly
Dr. Jill
Hi. I have a question. My blood test for B-12 always comes back high- like 1600 or so. I don’t eat any meat except chicken or fish. When I have taken b-12 supplements in the past, they have always made me feel better. Why is this if my blood tests always run high? Could my body still be depleted even with levels as high as 1600? Thank you!
Hi Allie,
Serum B12 is not a great marker of intracellular status. There are many reasons why a person could have elevated serum B12 and low B12 getting into the cells. Serum or urine MMA is a more accurate marker of B12 – so yes, it’s possible that you could still be depleted.
Warmly
Dr Jill
I had the 23 and me genetic test. How do I determine from the raw data if I have the MTHFR variants?
Thanks for your help!
Hi Marcia
You will need to run data through third party, like Genetic Genie
warmly
Dr Jill
Dear Dr. Jill. Greetings from New Brunswick, Canada. You have written some very powerful stuff in the past, and this is a true eye opener. I’ve been inactive and very ill for the past 8 years. I was told I have CFS/FM, but mostly referred to as a hypochondriac, anorexic or lazy patient. I will discuss this with my new doctor (a N.D.). Keep on doing your amazing work. Those suffering in silence truly appreciate it!
Fascinating information – thank you so much!
I too am in New Brunswick, Canada and have just ordered my 23andMe kit. I wanted to ask if you have any resource recommendations on the East Coast of Canada. My son is working with a N.D. in Lower Sackville, NS after discovering he is 1298 – A:C heterozygous 677 – A:C heterozygous.
Manon, I’m interested in your new N.D. in NB.
Hi Suzy, Try searching for a doc to help at http://www.functionalmedicine.org
best
Dr Jill
Hi Dr. Jill; I’m glad to find this website! I’m a 45 yr old woman who had a massive stroke when I was 16. I was smoking & taking birth control pills at the time, so the docs finally decided that it was simply that — I was the anomaly. Because of my stroke, I developed epilepsy, & had to go on Tegretol. I had one child, who is relatively healthy at 18. However, when I was 42, I started getting rheumatoid arthritis.
I tried the traditional meds first, then switched to LDN. I was a vegetarian for about 10 years before my RA, but I became vegan. I’ve been a fitness fanatic all of my adult life, & I’m still gymming it, though not nearly enough. I started taking many supplements. It slowed the RA down, but didn’t vanquish it.
So I tested everything that I could think of: my gut is supremely healthy, I don’t have Lyme, cytomegalovirus, Epstein-barr, or candida.
I DO have two heterozygous variants of c677t & a1298c of the MTHFR gene… My integrative doc suggested B-complex with methyfolate. It didn’t help much, except to lower my anemia. I did start taking taurine (2500mg) & am feeling better than in a long while.
Is taurine working with the b-complex to help, or am I imagining this?
Can you suggest the best B-complex brand? Or should I take shots?
More suggestions?
Thank you!!!
Hi Aja,
Unfortunately with treating these issues, it must be individualized to the patients and treating just the methylation SNPs does not work. However, my favorite general active B vitamin is Prothera Active B Complex, which you can order from Prothera with code: 618. I also like the Prothera Methy-B12 lozenger.
Warmly
Dr. Jill
Hi Jill, I live in South Florida (Ft. Lauderdale) and would you know any physician who could perform MTHF mutation testing or at least be familiar with it?
Hi Alex
Search by zip code at http://www.functionalmedicine.org
blessings
Dr Jill
I am homozygous for 677 and have been supplementing with Thorne Methyl-Guard Plus (1/day) and Thorne Basic Nutrients for 2 years. My serum folate levels just came back >24ng/mL. Can activated methylfolate raise those levels? I don’t get any synthetic folic acid in supplements or diet so I am confused as to why that level is so high. I thought it was measuring folic acid not the biologically usable form. Is that folate level too high? Thanks so much! Blessings!
Hi Jen,
this may be because your body is unable to use the regular folate and it is accumulating in your serum
Dr Jill
Would you cut back on the methyl guard and just use a multi-vitamin with methylfolate and methyl cobalamin for B vitamins? My B12 was slightly high (1200 pg/mL) and homocysteine fine (5.9 umol/L). I am assuming by “regular folate” you mean l-methylfolate. Thank you!
Hi Jen
I cannot give you medical advice on the blog. Please consult with your physician.
warmly
Dr Jill
Ok! But it is possible the good folate is showing up in my serum and not unmetabolized folic acid? You are amazing to read and follow, by the way! A true inspiration.
Thanks for the post! It helps everyone to understand something about MTHFR and methylation in general. In my opinion, 23andme is an excellent SNP DNA test kit and great value for the money. It went down from a one time fee of $199 to the current $99 USD.
Yes, unfortunately they raised the cost since I wrote the blog…
What are the alternatives to 23and me? I have factors which led me to wanting to identify my MTHFR genes. I have very high serum folate, had healthy births when I only started taking folic acid after I found out I was pregnant, miscarried the time I took folic acid few months in advance of conception, became ill after Trimethoprim anitbiotics (I read this could be related to mTHFR, but not sure) and others….
However, my saliva sample was rejected twice as 23and me were unable to get enough DNA from my saliva. They have now said I cannot order from them again! 🙁
But I don want to find out about MTHFR, especially since I want to have at least one more child. What can I do?
I recommend 23andme for the cost. There are other speciality labs but much more expensive. For just MTHFR gene mutations, this can be ordered through any lab
Why not just test for Homocysteine levels? If high, then treat for it… if not… no problem. Right? Or am I missing something? I have what appears to be many symptoms of “overmethylation”… any suggestions? Thanks!!
Yes, this is an important marker for sure but there are many others.
I agree with you
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